10-99329434-G-C

Variant names:

• chr10-99329434-G-C
• rs764714273
• NM_020348.3:c.47G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020348.3(CNNM1):​c.47G>C​(p.Arg16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 1,042,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R16Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: CNNM1 NM_020348.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345
• Publications: 0 publications found

Genes affected

CNNM1 (HGNC:102): (cyclin and CBS domain divalent metal cation transport mediator 1) This gene encodes a member of the ancient conserved domain protein family. The encoded protein may bind copper. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25575408).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020348.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM1	NM_020348.3	MANE Select	c.47G>C	p.Arg16Pro	missense	Exon 1 of 11	NP_065081.2	Q9NRU3-1
	CNNM1	NM_001345887.2		c.47G>C	p.Arg16Pro	missense	Exon 1 of 12	NP_001332816.1	A0A8Q3SIV9
	CNNM1	NM_001345889.2		c.47G>C	p.Arg16Pro	missense	Exon 1 of 11	NP_001332818.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM1	ENST00000356713.5	TSL:1 MANE Select	c.47G>C	p.Arg16Pro	missense	Exon 1 of 11	ENSP00000349147.4	Q9NRU3-1
	CNNM1	ENST00000696687.1		c.47G>C	p.Arg16Pro	missense	Exon 1 of 12	ENSP00000512809.1	A0A8Q3SIV9
	CNNM1	ENST00000914274.1		c.47G>C	p.Arg16Pro	missense	Exon 1 of 10	ENSP00000584333.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000192 AC: 2 AN: 1042442 Hom.: 0 Cov.: 13 AF XY: 0.00000191 AC XY: 1 AN XY: 522862

African (AFR) AF: 0.00 AC: 0 AN: 21024

American (AMR) AF: 0.00 AC: 0 AN: 23964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19524

East Asian (EAS) AF: 0.00 AC: 0 AN: 28600

South Asian (SAS) AF: 0.0000160 AC: 1 AN: 62526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3442

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 798922

Other (OTH) AF: 0.00 AC: 0 AN: 45714

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.017
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.34
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.080	N
REVEL	Uncertain	0.54
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.27	T
Polyphen		0.97	D
Vest4		0.19
MutPred		0.32		Loss of MoRF binding (P = 0.0115)
MVP		0.45
ClinPred		0.57	D
GERP RS		3.0
PromoterAI		-0.030	Neutral
Varity_R		0.37
gMVP		0.72
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs764714273; hg19: chr10-101089191;